An epigenetic clock for gestational age at birth based on blood methylation data

Anna K. Knight, Jeffrey M. Craig, Christiane Theda, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine S. Hansen, Mads V. Hollegaard, David M. Hougaard, Preben B. Mortensen, Shantel M. Weinsheimer, Thomas M. Werge, Patricia A. Brennan, Joseph F. Cubells, D. Jeffrey Newport, Zachary N. Stowe, Jeanie L Y Cheong, Philippa Dalach, Lex W. Doyle, Yuk J. Loke, Andrea A. Baccarelli & 27 others Allan C. Just, Robert O. Wright, Mara M. Téllez-Rojo, Katherine Svensson, Letizia Trevisi, Elizabeth M. Kennedy, Elisabeth B. Binder, Stella Iurato, Darina Czamara, Katri Räikkönen, Jari M T Lahti, Anu Katriina Pesonen, Eero Kajantie, Pia M. Villa, Hannele Laivuori, Esa Hämäläinen, Hea Jin Park, Lynn B. Bailey, Sasha E. Parets, Varun Kilaru, Ramkumar Menon, Steve Horvath, Nicole R. Bush, Kaja Z. LeWinn, Frances A. Tylavsky, Karen N. Conneely, Alicia K. Smith

Research output: Contribution to journalArticle

Abstract

Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

Original languageEnglish (US)
Article number206
JournalGenome Biology
Volume17
Issue number1
DOIs
StatePublished - Oct 7 2016
Externally publishedYes

Fingerprint

gestational age
methylation
Epigenomics
epigenetics
Methylation
Gestational Age
blood
DNA methylation
DNA Methylation
Parturition
DNA
Fetal Blood
Proxy
birth weight
ancestry
researchers
developmental stage
testing
Research Personnel
developmental stages

Keywords

  • Aging
  • Biomarker
  • Birthweight
  • Blood spot
  • Cord blood
  • Developmental age
  • DNA methylation
  • Epigenetic clock
  • Fetus
  • Medicaid
  • Preterm birth
  • Socioeconomic status

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Cite this

Knight, A. K., Craig, J. M., Theda, C., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hansen, C. S., ... Smith, A. K. (2016). An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biology, 17(1), [206]. https://doi.org/10.1186/s13059-016-1068-z

An epigenetic clock for gestational age at birth based on blood methylation data. / Knight, Anna K.; Craig, Jeffrey M.; Theda, Christiane; Bækvad-Hansen, Marie; Bybjerg-Grauholm, Jonas; Hansen, Christine S.; Hollegaard, Mads V.; Hougaard, David M.; Mortensen, Preben B.; Weinsheimer, Shantel M.; Werge, Thomas M.; Brennan, Patricia A.; Cubells, Joseph F.; Newport, D. Jeffrey; Stowe, Zachary N.; Cheong, Jeanie L Y; Dalach, Philippa; Doyle, Lex W.; Loke, Yuk J.; Baccarelli, Andrea A.; Just, Allan C.; Wright, Robert O.; Téllez-Rojo, Mara M.; Svensson, Katherine; Trevisi, Letizia; Kennedy, Elizabeth M.; Binder, Elisabeth B.; Iurato, Stella; Czamara, Darina; Räikkönen, Katri; Lahti, Jari M T; Pesonen, Anu Katriina; Kajantie, Eero; Villa, Pia M.; Laivuori, Hannele; Hämäläinen, Esa; Park, Hea Jin; Bailey, Lynn B.; Parets, Sasha E.; Kilaru, Varun; Menon, Ramkumar; Horvath, Steve; Bush, Nicole R.; LeWinn, Kaja Z.; Tylavsky, Frances A.; Conneely, Karen N.; Smith, Alicia K.

In: Genome Biology, Vol. 17, No. 1, 206, 07.10.2016.

Research output: Contribution to journalArticle

Knight, AK, Craig, JM, Theda, C, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hansen, CS, Hollegaard, MV, Hougaard, DM, Mortensen, PB, Weinsheimer, SM, Werge, TM, Brennan, PA, Cubells, JF, Newport, DJ, Stowe, ZN, Cheong, JLY, Dalach, P, Doyle, LW, Loke, YJ, Baccarelli, AA, Just, AC, Wright, RO, Téllez-Rojo, MM, Svensson, K, Trevisi, L, Kennedy, EM, Binder, EB, Iurato, S, Czamara, D, Räikkönen, K, Lahti, JMT, Pesonen, AK, Kajantie, E, Villa, PM, Laivuori, H, Hämäläinen, E, Park, HJ, Bailey, LB, Parets, SE, Kilaru, V, Menon, R, Horvath, S, Bush, NR, LeWinn, KZ, Tylavsky, FA, Conneely, KN & Smith, AK 2016, 'An epigenetic clock for gestational age at birth based on blood methylation data', Genome Biology, vol. 17, no. 1, 206. https://doi.org/10.1186/s13059-016-1068-z
Knight AK, Craig JM, Theda C, Bækvad-Hansen M, Bybjerg-Grauholm J, Hansen CS et al. An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biology. 2016 Oct 7;17(1). 206. https://doi.org/10.1186/s13059-016-1068-z
Knight, Anna K. ; Craig, Jeffrey M. ; Theda, Christiane ; Bækvad-Hansen, Marie ; Bybjerg-Grauholm, Jonas ; Hansen, Christine S. ; Hollegaard, Mads V. ; Hougaard, David M. ; Mortensen, Preben B. ; Weinsheimer, Shantel M. ; Werge, Thomas M. ; Brennan, Patricia A. ; Cubells, Joseph F. ; Newport, D. Jeffrey ; Stowe, Zachary N. ; Cheong, Jeanie L Y ; Dalach, Philippa ; Doyle, Lex W. ; Loke, Yuk J. ; Baccarelli, Andrea A. ; Just, Allan C. ; Wright, Robert O. ; Téllez-Rojo, Mara M. ; Svensson, Katherine ; Trevisi, Letizia ; Kennedy, Elizabeth M. ; Binder, Elisabeth B. ; Iurato, Stella ; Czamara, Darina ; Räikkönen, Katri ; Lahti, Jari M T ; Pesonen, Anu Katriina ; Kajantie, Eero ; Villa, Pia M. ; Laivuori, Hannele ; Hämäläinen, Esa ; Park, Hea Jin ; Bailey, Lynn B. ; Parets, Sasha E. ; Kilaru, Varun ; Menon, Ramkumar ; Horvath, Steve ; Bush, Nicole R. ; LeWinn, Kaja Z. ; Tylavsky, Frances A. ; Conneely, Karen N. ; Smith, Alicia K. / An epigenetic clock for gestational age at birth based on blood methylation data. In: Genome Biology. 2016 ; Vol. 17, No. 1.
@article{83d8eae73d58425d879e77f0b5ee6cee,
title = "An epigenetic clock for gestational age at birth based on blood methylation data",
abstract = "Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.",
keywords = "Aging, Biomarker, Birthweight, Blood spot, Cord blood, Developmental age, DNA methylation, Epigenetic clock, Fetus, Medicaid, Preterm birth, Socioeconomic status",
author = "Knight, {Anna K.} and Craig, {Jeffrey M.} and Christiane Theda and Marie B{\ae}kvad-Hansen and Jonas Bybjerg-Grauholm and Hansen, {Christine S.} and Hollegaard, {Mads V.} and Hougaard, {David M.} and Mortensen, {Preben B.} and Weinsheimer, {Shantel M.} and Werge, {Thomas M.} and Brennan, {Patricia A.} and Cubells, {Joseph F.} and Newport, {D. Jeffrey} and Stowe, {Zachary N.} and Cheong, {Jeanie L Y} and Philippa Dalach and Doyle, {Lex W.} and Loke, {Yuk J.} and Baccarelli, {Andrea A.} and Just, {Allan C.} and Wright, {Robert O.} and T{\'e}llez-Rojo, {Mara M.} and Katherine Svensson and Letizia Trevisi and Kennedy, {Elizabeth M.} and Binder, {Elisabeth B.} and Stella Iurato and Darina Czamara and Katri R{\"a}ikk{\"o}nen and Lahti, {Jari M T} and Pesonen, {Anu Katriina} and Eero Kajantie and Villa, {Pia M.} and Hannele Laivuori and Esa H{\"a}m{\"a}l{\"a}inen and Park, {Hea Jin} and Bailey, {Lynn B.} and Parets, {Sasha E.} and Varun Kilaru and Ramkumar Menon and Steve Horvath and Bush, {Nicole R.} and LeWinn, {Kaja Z.} and Tylavsky, {Frances A.} and Conneely, {Karen N.} and Smith, {Alicia K.}",
year = "2016",
month = "10",
day = "7",
doi = "10.1186/s13059-016-1068-z",
language = "English (US)",
volume = "17",
journal = "Genome Biology",
issn = "1474-7596",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - An epigenetic clock for gestational age at birth based on blood methylation data

AU - Knight, Anna K.

AU - Craig, Jeffrey M.

AU - Theda, Christiane

AU - Bækvad-Hansen, Marie

AU - Bybjerg-Grauholm, Jonas

AU - Hansen, Christine S.

AU - Hollegaard, Mads V.

AU - Hougaard, David M.

AU - Mortensen, Preben B.

AU - Weinsheimer, Shantel M.

AU - Werge, Thomas M.

AU - Brennan, Patricia A.

AU - Cubells, Joseph F.

AU - Newport, D. Jeffrey

AU - Stowe, Zachary N.

AU - Cheong, Jeanie L Y

AU - Dalach, Philippa

AU - Doyle, Lex W.

AU - Loke, Yuk J.

AU - Baccarelli, Andrea A.

AU - Just, Allan C.

AU - Wright, Robert O.

AU - Téllez-Rojo, Mara M.

AU - Svensson, Katherine

AU - Trevisi, Letizia

AU - Kennedy, Elizabeth M.

AU - Binder, Elisabeth B.

AU - Iurato, Stella

AU - Czamara, Darina

AU - Räikkönen, Katri

AU - Lahti, Jari M T

AU - Pesonen, Anu Katriina

AU - Kajantie, Eero

AU - Villa, Pia M.

AU - Laivuori, Hannele

AU - Hämäläinen, Esa

AU - Park, Hea Jin

AU - Bailey, Lynn B.

AU - Parets, Sasha E.

AU - Kilaru, Varun

AU - Menon, Ramkumar

AU - Horvath, Steve

AU - Bush, Nicole R.

AU - LeWinn, Kaja Z.

AU - Tylavsky, Frances A.

AU - Conneely, Karen N.

AU - Smith, Alicia K.

PY - 2016/10/7

Y1 - 2016/10/7

N2 - Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

AB - Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

KW - Aging

KW - Biomarker

KW - Birthweight

KW - Blood spot

KW - Cord blood

KW - Developmental age

KW - DNA methylation

KW - Epigenetic clock

KW - Fetus

KW - Medicaid

KW - Preterm birth

KW - Socioeconomic status

UR - http://www.scopus.com/inward/record.url?scp=84990848178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990848178&partnerID=8YFLogxK

U2 - 10.1186/s13059-016-1068-z

DO - 10.1186/s13059-016-1068-z

M3 - Article

VL - 17

JO - Genome Biology

JF - Genome Biology

SN - 1474-7596

IS - 1

M1 - 206

ER -